Scientific Publications by FDA Staff

Infect Immun 2005 Sep;73(9):6091-100

Genome-wide expression profiling in malaria infection reveals transcriptional changes associated with lethal and nonlethal outcomes.

Schaecher K, Kumar S, Yadava A, Vahey M, Ockenhouse CF

Ockenhouse CF, Walter Reed Army Inst Res, Dept Immunol, 503 Robert Grant Ave, Silver Spring, MD 20910 USA Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD 20910 USA Walter Reed Army Inst Res, Div Communicable Dis & Immunol, Silver Spring, MD 20910 USA Walter Reed Army Inst Res, Div Retrovirol, Silver Spring, MD 20910 USA US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA

High-density oligonucleotide microarrays are widely used to study gene expression in cells exposed to a variety of pathogens. This study addressed the global genome-wide transcriptional activation of genes in hosts infected in vivo, which result in radically different clinical outcomes. We present an analysis of the gene expression profiles that identified a set of host biomarkers which distinguish between lethal and nonlethal blood stage Plasmodium yoelii malaria infections. Multiple biological replicates sampled during the course of infection were used to establish statistically valid sets of differentially expressed genes. These genes that correlated with the intensity of infection were used to identify pathways of cellular processes related to metabolic perturbations, erythropoiesis, and B-cell immune responses and other innate and cellular immune responses. The transcriptional apparatus that controls gene expression in erythropoiesis was also differentially expressed and regulated the expression of target genes involved in the host's response to malaria anemia. The biological systems approach provides unprecedented opportunities to explore the pathophysiology of host-pathogen interactions in experimental malaria infection and to decipher functionally complex networks of gene and protein interactions.